Acetic Acid → tert-butyl {(5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-yl}carbamate

HRID 340176Notes

Reaction equation

HRID 340176 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH3:20])[NH:10][C:9]1=[N:21][NH2:22])([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]([F:33])([F:32])[C:26]1([C:29](O)=O)[CH2:28][CH2:27]1.ON1C2N=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].C(O)(=O)C>ClCCl.C(#N)C>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:11]([CH3:20])[N:10]2[C:29]([C:26]3([C:25]([F:33])([F:32])[F:24])[CH2:28][CH2:27]3)=[N:22][N:21]=[C:9]12)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 769Bicarbonate Ion2×HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acidHCID 178461610HCID 178461610, compound

Product 1

HCID 86698236tert-butyl {(5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-yl}carbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude tert-butyl[(3S,5S,6R)-2-hydrazinylidene-6-methyl-5-phenylpiperidin-3-yl]carbamate (99 mg, 0.31 mmol) in dichloromethane (3.1 mL) was added 1-(trifluoromethyl)cyclopropanecarboxylic acid (58 mg, 0.37 mmol), 1-hydroxy-7-azabenzotriazole (4.3 mg, 0.031 mmol), N-methylmorpholine (82 μL, 0.75 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.37 mmol). The mixture was stirred 1 h. Saturated aqueous bicarbonate was added, and the resulting mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Acetonitrile (12.5 mL) and glacial acetic acid (18 μL, 0.31 mmol) were added and the resulting mixture stirred at 70° C. for 90 min. Saturated aqueous bicarbonate was added, and the resulting mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated giving the crude title compound. MS 437.2 (M+1),

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringthe resulting mixture stirred at 70° C. for 90 min
  7. extractionthe resulting mixture was extracted with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-dc085fd097424129ae374446d7ae38d7
Source dataset
uspto-grants-2014_11
Patent number
US08895572B2

Reaction notes

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